HPLC测定复方盐酸多塞平胶囊中盐酸多塞平与盐酸可乐定的含量

采用高效液相色谱法测定复方盐酸多塞平胶囊中盐酸多塞平与盐酸可乐定的含量。盐酸多塞平在５～３０μｇ／ｍｌ（ｒ＝０９９９８），盐酸可乐定在２～１２μｇ／ｍｌ（ｒ＝０９９９９）范围内，峰面积与其浓度呈良好线性关系；方法平均回收率分别为１００１８％（ＲＳＤ＝１０２％），１００３４％（ＲＳＤ＝１６３％）。结果表明，方法简便、快速、准确。     

LC-MS2法鉴别菊花槐米胶囊中掺加的尼群地平成分

目的:建立菊花槐米胶囊中非法掺加尼群地平成分的鉴别方法。方法:采用色谱柱C18(250 mm×2.0 mm);乙腈-水(50∶50)为流动相;流速:0.2 mL.min-1;采用电喷雾离子化(ESI)方式;二级质谱母离子m/z359,碰撞能量20 V。结果:在高效液相色谱、质谱中,样品出现与尼群地平成分一致的色谱峰、质谱峰。结论:本方法简单可行,结果准确可靠,可用于菊花槐米胶囊中掺加尼群地平成分的定性鉴别。     

LC-MS2法鉴别菊花槐米胶囊中掺加的尼群地平成分

目的：建立菊花槐米胶囊中非法掺加尼群地平成分的鉴别方法。方法：采用色谱柱C18（250mm×2．0mm）；乙腈-水（50：50）为流动相；流速：0．2mL·min^-1；采用电喷雾离子化（ESI）方式；二级质谱母离子m／z359，碰撞能量20V。结果：在高效液相色谱、质谱中，样品出现与尼群地平成分一致的色谱峰、质谱峰。结论：本方法简单可行，结果准确可靠，可用于菊花槐米胶囊中掺加尼群地平成分的定性鉴别。     

舒肝解郁胶囊联合盐酸多塞平治疗血管性头痛的临床疗效

目的对舒肝解郁胶囊联合盐酸多塞平片治疗血管性头痛的疗效进行观察。方法选取2010年3月至2014年8月期间,我院门诊诊治的血管性头痛患者104例(观察组)作为试验对象,让观察组成员接受舒肝解郁胶囊以及盐酸多塞平治疗,而让对照组102例患者接受盐酸多赛平治疗。结果观察组总有效率为94.23%,其中显效率73.08%;对照组总有效率为75.49%,其中显效率36.27%。两组相比总有效率有非常显著差异(χ~2=33.39 P<0.001),显效率也有非常显著的差异(χ~2=28.16,P<0.001)。治疗期间未见明显不良反应情况发生。结论舒肝解郁胶囊联合盐酸多塞平片对血管性头痛疗效明显优于单用盐酸多塞平片,又充分发挥了盐酸多塞平片作用于体内特异受体的优势,二者合用,优势互补,在提高疗效的同时减轻了不良反应。     

LC/MS/MS法同时测定细胞孵化液中6种雌激素类化合物的含量

目的建立同时测定细胞孵化液中6种雌激素类化合物含量的LC/MS/MS法,并用该法研究E1S在乳腺癌细胞中的代谢行为。方法细胞孵化样品经处理后,采用Diamonsil C18柱分离,流动相为乙腈和5 mmol.L-1醋酸铵(pH 7.8),梯度洗脱,采用电喷雾电离(electrospray ionization,ESI)源,以多反应监测(multiple reaction monitoring,MRM)方式进行检测,用于定量分析的离子反应分别为m/z 269.3→m/z 145.2(雌酮,estrone,E1),m/z 271.1→m/z 145.2(雌二醇,estradiol,E2),m/z349.2→m/z 269.2(硫酸雌酮e,strone-3-sulfate,E1S),m/z 351.1→m/z 271.3(硫酸雌二醇,estradiol-3sulfate,E2S),m/z 445.5→m/z 269.3(β-D-葡萄糖醛酸雌酮,estrone-3-glucuronide,E1G),m/z 447.4→m/z 271.0(葡萄糖醛酸雌二醇,estradiol-3-glucuronide,E2G)和m/z 253.4→m/z 223.0(大豆苷元,内标)。结果该方法中E1、E2、E1S、E2S的线性分别为9.8～5 000.0 nmol.L-1,E1G、E2G的线性为0.98～500.00 nmol.L-1;日内和日间精密度均小于10.8%,相对误差在±11.7%以内。结论该法适用于细胞孵化液中6种雌激素类化合物的同时测定。     

3种方法测定伪麻黄碱血药浓度的比较研究

目的 建立并比较测定伪麻黄碱血药浓度的HPLC法、柱前衍生-HPLC法和LC/MS/MS法,为体内低浓度伪麻黄碱的分析提供更为简便、准确的方法.方法 摸索并优化血浆前处理条件、衍生化条件、色谱条件、质谱条件等.结果 3种方法均具有较好的专属性、线性、精密度、回收率和稳定性,可准确、灵敏地检测生物样本中的伪麻黄碱.3种方...     

盐酸头孢卡品酯片在中国健康受试者体内的药动学

目的研究中国健康受试者单/多次口服盐酸头孢卡品酯片的药动学。方法将30例受试者随机分为3组,每组10例,男女各半,一组进行盐酸头孢卡品酯片低剂量（100 mg）的单/多次给药人体药动学试验,受试者每天服药3次,每次100 mg,一共服药12次;一组进行盐酸头孢卡品酯片中剂量（200 mg）的单次给药人体药动学试验;一组进行盐酸头孢卡品酯片高剂量（300 mg）的单次给药人体药动学试验。采用高效液相色谱 串联质谱（HPLC MS/MS）法测定活性代谢产物头孢卡品的血浓度,采用DAS 2.0版软件计算其主要药动学参数,采用SPSS 17.0版软件对主要参数进行统计分析。结果单次空腹口服盐酸头孢卡品酯片100,200和300 mg后主要药动学参数：tmax分别为（1.42±0.54）,（1.80±0.59）和（2.10±0.81） h;t1/2分别为（1.45±0.17）,（1.60±0.22）和（1.44±0.18） h;MRT0 12 h分别为（2.75±0.42）,（2.99±0.33）和（3.31±0.57） h;Cmax分别为（1 419±384）,（2 128±366）和（2 438±655） μg&#8226;L－1;AUC0 12 h分别为（4 369±1 078）,（7 477±1 616）和（9 091±3 735） μg&#8226;h&#8226;L－1;AUC0 ∞分别为（4 389±1 080）,（7 528±1 640）和（9 146±3 749） μg&#8226;h&#8226;L－1;V/F分别为（52.13±21.81）,（63.60±14.78）和（76.06±23.29） L;CL/F分别为（24.27±7.06）,（27.61±5.42）和（36.49±10.31） L&#8226;h－1。多次口服盐酸头孢卡品酯片100 mg后主要药动学参数：tmax为（1.90±0.70） h;t1/2为（1.63±0.16） h;MRT0 12 h为（2.87±0.52） h;Cssmax为（1 133±200） μg&#8226;L－1;AUCss为（3 607±730） μg&#8226;h&#8226;L－1;AUC0 12 h为（3 731±775） μg&#8226;h&#8226;L－1;AUC0 ∞为（3 757±785） μg&#8226;h&#8226;L－1;V/F为（66.15±20.29） L;CL/F为（27.85±6.66） L&#8226;h－1,Cssmin为（105.4±57.17） μg&#8226;L－1;Cav为（450.9±91.2） μg&#8226;L－1;DF为（2.33±0.47）;观察蓄积比Ro为（0.870±0.131）。结论盐酸头孢卡品酯片在剂量为100～300 mg范围内呈线性药动学特征,口服盐酸头孢卡品酯片,每日3次,每次100 mg,未发现蓄积现象。     

UPLC-Q-TOF/MS同时测定强力天麻杜仲胶囊中5种成分的含量

目的 建立UPLC-Q-TOF/MS同时测定强力天麻杜仲胶囊中天麻素、京尼平苷酸、松脂醇二葡萄苷、苯甲酰新乌头原碱及蛇床子素含量的方法。方法 采用Waters ACQUITY UPLC,色谱柱为CORTECSTM C₁₈柱（4.6 mm×150 mm,2.7 μm）,流动相为乙腈（A）-0.1%甲酸水溶液（B）梯度洗脱,电喷雾离子源（ESI）,正负离子模式,质量扫描范围为50~1 200 Da。结果 5种被测成分在线性范围内均具有良好的线性关系（r² ≥ 0.997 4）,平均回收率在99.533%~107.525%,RSD ≤ 2.56%。结论 应用UPLC-Q-TOF/MS法分离效果及重复性好,且快速、简便,可作为强力天麻杜仲胶囊的质量控制方法。     

降糖保健食品中非法添加盐酸苯乙双胍和格列本脲的检测

目的:建立检测降糖保健食品中非法添加化学成分盐酸苯乙双胍和格列本脲的定性、定量检测方法.方法:采用薄层色谱法、高效液相色谱-二极管阵列检测法、LC/MS/MS联用技术进行定性鉴别,并采用高效液相色谱法测定其中盐酸苯乙双胍和格列本脲的含量.结果:在抽取的9种市售样品中,有3种检出了盐酸苯乙双胍和格列本脲,1#～3#阳性样品中添加的盐酸苯乙双胍和格列本脲分别为8.54、6.51、10.53 mg/g和6.01、4.04、2.70 mg/g.结论:该方法快速、准确、灵敏、可靠,可用于有效监测保健食品中非法添加的盐酸苯乙双胍和格列本脲.     

动态文本分类中概念漂移问题的解决算法研究

以当前的"消极学习型分类法"加"动态更新训练集"的组合模式,不足以解决好动态文本分类中的概念漂移问题.为此,受消极分类法基本思想的启发,并借鉴k-NN算法的优点,提出了针对概念漂移问题的"消极特征选择模式"的概念和基于此模式的动态文本分类算法.测试结果表明,新算法很好地解决了当前存在的难点问题,具有高可靠性、高实用性等优点.     

Predictive strategy for the rapid structure elucidation of drug degradants

Structural information on drug degradants and impurities can serve to accelerate the drug discovery and development cycle. Traditional structure elucidation methodologies for obtaining this information are often slow and resource-consuming; therefore, LC/MS profiling and LC/MS/MS substructural analysis methodologies have been developed to rapidly and accurately elucidate structures of impurities and degradants. This work is a further development of methodologies used for the elucidation of degradation products of paclitaxel [K.J. Volk et al., Proc. 9th AAPS Ann. Meeting, 1994, p. 29]. In this study cefadroxil was used as a model compound for the evaluation of a predictive strategy for the production and elucidation of impurities and degradants induced by acid, base, and heat, using LC/MS and LC/MS/MS profiling methodology, resulting in an LC/MS degradant database which includes information on molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. Furthermore, libraries such as this can provide a predictive foundation for pre-clinical development work involving drug stability, synthesis, and monitoring.     

LC/MS/MS与GC/MS法分析鉴定小鼠尿中沙美特罗的代谢产物

目的:鉴定沙美特罗在小鼠尿中的主要代谢产物.方法:ig给药后,收集小鼠尿液,经固相提取,葡萄糖醛酸酶水解,进行LC/MS/MS分析和硅烷化后进行GC/MS分析同时分离鉴定沙美特罗代谢产物.结果和结论:在给药后尿样中发现沙美特罗原型和4种代谢产物M1～M4,其结构推测为19-羟基沙美特罗(M1)、2-羰基沙美特罗(M2)、19-羰基沙美特罗(M3)和19-羟基-8-甲氧基沙美特罗(M4).     

Establishment of a liquid chromatographic/mass spectrometry method for quantification of tetrandrine in rat plasma and its application to pharmacokinetic study

A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC/MS/MS) for the determination of tetrandrine in rat plasma has been developed, fully validated and successfully applied to pharmacokinetic study in Sprague-Dawley (SD) rats after a single oral administration. Sample preparation involves a liquid-liquid extraction with n-hexane-dichlormethane (65:35, containing 1% 2-propanol isopropyl alcohol, v/v). Tetrandrine and brodimoprim (internal standard) were well separated by LC with a Dikma C(18) column using acetonitrile-methanol-ammonium formate aqueous solution (20mM) containing 0.3% formic acid (20:30:50, v/v/v) as mobile phase. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 623.0-->381.0 and m/z 339.0-->281.0 for tetrandrine and I.S., respectively. The present method exhibited good linearity over the concentration range of 5-2,000 ng/mL for tetrandrine in rat plasma with a lower limit of quantification of 5 ng/mL. The intra- and inter-day precision were 2.0-9.2% and 4.5-9.4%, and the intra- and inter-day accuracy ranged from -7.6 to 10.3% and -6.0 to 5.3%, respectively. No endogenous compounds were found to interfere with the analysis, and tetrandrine was stable during the whole assay period. The method was successfully applied to a pharmacokinetic study after an intragastric administration (i.g.) of tetrandrine to SD rats with a single dose of 50mg/kg. The results confirm that the assay is suitable for the pharmacokinetic study of tetrandrine.     

脉络宁注射液中绿原酸在健康人体内的药动学

目的：研究单剂量和多剂量静脉滴注脉络宁注射液中绿原酸在健康人体内的药动学。方法：10名健康受试者单、多次剂量静脉滴注脉络宁注射液后,采用高效液相色谱．质谱联用法（LC／MS／MS）测定血浆中绿原酸浓度,DAS（1．0）软件对其药．时曲线进行拟合,并计算药动学参数。结果：绿原酸药．时曲线符合二房室模型,单、多次剂量主要药动学参数分别为Cmax：（252±66）、（262±87）μg／L;t1/2β：（1．35±0．53）、（1．37±0．27）h;V：（0．70±0．24）、（0．68±0．24）L／kg;CL：（0．37±0．10）、（0．34±0．11）L·kg^-1·h^-1;AUG0-tn：（404±110）、（455±151）μg·L^-1·h。结论：单剂量和多次静脉滴注脉络宁注射液后绿原酸主要药动学参数经统计学处理差异无统计学意义;连续多次给药后,绿原酸体内无蓄积现象,绿原酸的体内过程不受性别差异的影响。     

Liquid chromatography-tandem mass spectrometry for the determination of jaceosidin in rat plasma

Jaceosidin (4′,5,7-trihydroxy–3′,6-dimethoxyflavone), isolated from Artemisia species as well as Eupatorium species, has antiallergic, anticancer, anti-inflammatory and antioxidant activity. A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the quantification of jaceosidin in rat plasma was developed to characterize the pharmacokinetics of jaceosidin. Jaceosidin and the internal standard, linezolid, were extracted from rat plasma with ethyl acetate at acidic pH and analyzed on a Luna phenyl-hexyl column using the mixture of acetonitrile and 0.1% formic acid (45:55, v/v) as a mobile phase. The analytes were determined using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The calibration curve was linear (r² = 0.9973) over the concentration range of 2.00–500 ng/ml. The lower limit of quantification for jaceosidin was 2.0 ng/ml using 50 μl of plasma sample. The coefficients of variation of intra- and inter-assay at four QC levels were 2.4–9.6% and the relative errors were −9.1 to 10.0%. The matrix effects for jaceosidin and linezolid were practically absent. The recoveries of jaceosidin and linezolid were 87.0 and 87.7%, respectively. This method was successfully applied to the pharmacokinetic study of jaceosidin in rats.     

代谢组学分析技术平台和数据处理的新进展

分析技术和生物计量学促进了代谢组学的飞速发展。代谢组学快速、灵敏、可定量、非侵入性以及系统性的特点,使其在新药研发、药物毒性筛选、疾病诊断等领域显示出广阔的前景。本文综述了代谢组学研究中的某些关键问题:样品处理方法,分析技术和数据处理的方法和原则,代谢组动态变化、生物标记物的鉴定和代谢途径的检索近年来的进展。评价了各种分析手段的优缺点,并展望代谢组学发展前景。     

Strategy for identification of leachables in packaged pharmaceutical liquid formulations

Drug stability is one of the key properties to be monitored in pharmaceutical drug development. Drug degradation products, impurities and/or leachables from the drug product and packages may have significant impacts on drug efficacy, safety profile and storage conditions. In the registration stability samples of an ophthalmic pharmaceutical drug product, an unknown compound was found at a level of 0.19% by HPLC analysis. Subsequent liquid chromatography/mass spectrometry (LC/MS) analysis with electrospray ionization (ESI) indicated that the unknown was not related to the drug substance and was most likely a leachable. Identification of this unknown leachable was needed to evaluate the impact on drug safety. Through systematic extraction of various components or component combination of the packaging materials, and subsequently LC/MS analysis, the unknown was found to be a leachable coming from the varnish applied to the label. In general, using LC/MS alone is not sufficient to elucidate the structure of a complete unknown. Gas chromatography/mass spectrometry (GC/MS) was then conducted with a chemical ionization (CI) source to determine the retention time and mass of the compound of interest. Both CI and ESI sources generated the same protonated molecular ion [M+H] and similar fragmentation ions, which provides a good correlation of the unknown eluted in the liquid chromatogram and in the gas chromatogram. GC/MS with electron impact (EI) was then conducted to obtain the EI mass spectrum of this unknown. It was identified as monomethyl derivative of mephenesin through the NIST library search. The identification strategy utilized electrospray LC/MS and GC/MS with chemical and electron ionization sources which provided complimentary information for structure elucidation of this unknown compound. This combination approach in conjunction with systematic extraction was necessary for the determination of the source of this unknown in the pharmaceutical drug stability studies.     

PMEA-Na在beagle犬血浆中的液相色谱/质谱/质谱联用法测定及其药代动力学

目的建立LC/MS/MS法测定犬血浆中PMEA-Na浓度,进行其药代动力学研究.方法血浆样品经甲醇沉淀蛋白后,采用多反应监测法测定其血药浓度.色谱柱为Xterra MS柱,流动相为甲醇水甲酸(25750.5),流速为 0.25 ml·min-1.Beagle犬分3个剂量组经静脉给药,给药剂量分别为 1.0、3.0 和 6.0 mg·kg-1.药代动力学参数通过DAS软件计算获得.结果PMEA-Na线性范围0.02～20 mg·L-1 (r=0.999);最低检测浓度为 20 μg·L-1,方法回收率为 97.1%～107.3%,日内日间变异分别小于 6.5%、10.8%.beagle 犬在 1.0, 3.0 与 6.0 mg·kg-1剂量下单次iv PMEA-Na后,测得其AUC分别为 2.3±0.5, 8.2±1.3 and 18.5±1.3 mg·L-1·h; t1/2 为 3.9±1.8, 8.4±1.5 and 8.9±0.6 h; CL为 0.44±0.09, 0.35±0.05 and 0.31±0.03 ml·h-1·kg-1.结论本方法专属性强,准确性好,可用于PMEA-Na血药浓度测定和药代动力学研究.     

Validation of a sensitive LC/MS/MS method for simultaneous quantitation of flupentixol and melitracene in human plasma

A sensitive method has been developed and validated, using LC/ESI-MS/MS, for simultaneous quantitation of flupentixol and melitracen—antidepressant drugs, in human plasma. The quantitation of the target compounds was determined in a positive ion mode and multiple reaction monitoring (MRM). The method involved a repeated liquid–liquid extraction with diethyl ether and analytes were chromatographed on a C₈ chromatographic column by elution with acetonitrile–water–formic acid (36:64:1, v/v/v) and analyzed by tandem mass spectrometry. The method was validated over the concentration ranges of 26.1–2090 pg/ml for flupentixol and 0.206–4120 ng/ml for melitracen. The correlation coefficients of both analyst were >0.998 for six sets of calibration curves. The recovery was 60.9–75.1% for flupentixol, melitracen and internal standard. The lower limit of quantitation (LLOQ) detection was 26.1 pg/ml for flupentixol and 0.206 ng/ml for melitracen. Intra- and inter-day precision of the assay at three concentrations were 2.15–5.92% with accuracy of 97.6–103.0% for flupentixol and 0.5–6.36% with accuracy of 98.7–101.7% for melitracen. Stability of compounds was established in a battery of stability studies, i.e., bench-top, autosampler and long-term storage stability as well as freeze/thaw cycles. The method proved to be suitable for bioequivalence study of flupentixol and melitracen in healthy human male volunteers.     

An Adaptive Two-Stage Dose-Response Design Method for Establishing Proof of Concept

We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish “global” PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.